Use of Thickeners Versus Hydrolysed Formulae in the Management of Gastro-oesophageal Reflux Disease in Infants: A Systematic Review

Maram S. Albadi^1,

¹Department of Nutrition, Gynecology, Maternity and Children Hospital, Medina, KSA

Cite this paper:
Maram S. Albadi. Use of Thickeners Versus Hydrolysed Formulae in the Management of Gastro-oesophageal Reflux Disease in Infants: A Systematic Review. International Journal of Clinical Nutrition. 2021; 6(1):1-11. doi: 10.12691/ijcn-6-1-1

Abstract

Background and objective: Regurgitation symptoms in many GERD infants might affect their nutrition status. This review compares thickeners and hydrolysis formula with cow’s milk in the evolution of regurgitation, weight and stool consistency changes in infants with GERD based on currently available evidence, as the benefits of using AR-F in infants with GERD is still contradictory. There is also evidence that hydrolysed formula plays a crucial role in regulating reflux. Methods: The search terms ‘thickener formula/pre-thickener’ OR ‘cow’s milk allergy/hydrolysis formula’ AND ‘gastro-oesophageal reflux disease (GERD)/regurgitations’ were used to search the electronic databases of NUsearch, Google Scholar, ScienceDirect and PubMed for randomised controlled trials (RCTs) published between 2005 and 2020 for thickened formula and 2010-2020 for hydrolysed formula that involved infants (<13 months) of both sexes who were diagnosed or at risk of regurgitation. Results: Seven eligible RCTs met the inclusion criteria. Thickened whey protein formula significantly reduced daily regurgitations by up to 7.7 episodes, while the results were insignificant in thickened or normal extensive hydrolysed casein milk (-4.2 vs -3, respectively). However, rice thickener significantly reduced regurgitation and weight gain by 1.261 kg in two months. An insignificant difference in stool consistency was found in most trials (P >0.05), except for the thickened casein formula as 64% of participants had normal stool density (P= 0.45). Conclusion: This study identified that using either thickening formula or extensively hydrolysed formula significantly reduced the number of regurgitations per day (mean range: -1.2 to -7.1; P<0.05). It does, however, seem that hydrolysed whey formula thickened with hydrolysed rice can support weight gain in failure to thrive infants.

Keywords:
GERD regurgitation weight gain stool density

This work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

References:

[1]	Gonzalez Ayerbe, J. I., Hauser, B., Salvatore, S. and Vandenplas, Y. (2019). ‘Diagnosis and management of gastroesophageal reflux disease in infants and children: From guidelines to clinical practice’, Pediatric Gastroenterology, Hepatology & Nutrition, vol. 22, no. 2, p. 107.
[2]	Rosen, R., Vandenplas, Y., Singendonk, M., Cabana, M., DiLorenzo, C., Gottrand, F., Gupta, S., Langendam, M., Staiano, A., Thapar, N., Tipnis, N. and Tabbers, M. (2018). ‘Pediatric gastroesophageal reflux clinical practice guidelines: Joint recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN)’, Journal of Pediatric Gastroenterology and Nutrition, vol. 66, no. 3, p. 516-554.
[3]	Sherman, P. and Hassall, E. (2009). ‘A global, evidence-based consensus on the definition of gastroesophageal reflux disease (Gerd) in the pediatric population’, Paediatrics & Child Health, vol. 14, no. A, p. 26.
[4]	Jung H. K. (2011). ‘Epidemiology of gastroesophageal reflux disease in Asia: A systematic review’, Journal Neurogastroenterol Motility, vol. 17, no. 1, p. 14-27.
[5]	Dent, J., El-Serag, H. B., Wallander, M. A., Johansson, S. (2005). ‘Epidemiology of gastro-oesophageal reflux disease: A systematic review’, Gut, vol. 54, no. 5, p. 710-717.
[6]	Anand, I., Pentiuk, S., Garza, J., Su, W., Fei, L. and Kaul, A. (2020). ‘GER characteristics after fundoplication in children with aerodigestive disorders’, Journal of Pediatric Surgery, vol. 55, no. 3, p. 456-460.
[7]	Fernandez, S., Aspirot, A., Kerzner, B., Friedlander, J., Di Lorenzo, C. (2010). ‘Do some adolescents with rumination syndrome have “supragastric vomiting”?’, Journal of Pediatric Gastroenterol Nutrition, vol. 50, no. 1, p. 103-105.
[8]	Lightdale, J. R. and Gremse, D. A. (2013). ‘Gastroesophageal reflux: Management guidance for the paediatrician’, Pediatrics, vol. 131, no. 16, p. 84-95.
[9]	Orenstein, S. and McGowan, J. (2008). ‘Efficacy of Conservative Therapy as Taught in the Primary Care Setting for Symptoms Suggesting Infant Gastroesophageal Reflux’, The Journal of Pediatrics, vol. 152, no. 3, p .310-314.
[10]	Vandenplas, Y., Belli, D., Benhamou, P., Cadranel, S., Cezard, J., Cucchiara, S., Dupont, C., Faure, C., Gottrand, F., Hassall, E., Heymans, H., Kneepkens, C. and Sandhu, B. (1997). ‘A critical appraisal of current management practices for infant regurgitation - recommendations of a working party’, European Journal of Pediatrics, vol. 156, no. 5, p. 343-357.
[11]	Chak, A., Faulx, A., Eng, C., Grady, W., Kinnard, M., Ochs-Balcom, H. and Falk, G. (2006). ‘Gastroesophageal reflux symptoms in patients with adenocarcinoma of the oesophagus or cardia’, Cancer, vol. 107, no. 9, p. 2160-2166.
[12]	Mohammed, I., Cherkas, L. F., Riley, S. A., Spector, T. D. and Trudgill, N. J. (2003). ‘Genetic influences in gastro-oesophageal reflux disease: A twin study’, Gut, vol. 52, no. 8, p. 1085-1089.
[13]	Cameron, A. J., Lagergren, J., Henriksson, C., Nyren, O., Locke, G. R., Pedersen, N. L. (2002). ‘Gastroesophageal reflux disease in monozygotic and dizygotic twins’, Gastroenterology, vol. 122, no. 1, p. 55-59.
[14]	Van der Pol, R., Smits, M., van Wijk, M., Omari, T., Tabbers, M. and Benninga, M. (2011). ‘Efficacy of Proton-Pump Inhibitors in Children With Gastroesophageal Reflux Disease: A Systematic Review’, PEDIATRICS, vol. 127, no. 5, p. 925-935.
[15]	Corvaglia, L., Mariani, E., Aceti, A., Galletti, S. and Faldella, G. (2013). ‘Extensively hydrolyzed protein formula reduces acid gastroesophageal reflux in symptomatic preterm infants’, Early Human Development, vol. 89, no. 7, p. 453-455.
[16]	Salvatore, S., Savino, F., Singendonk, M., Tabbers, M., Benninga, M., Staiano, A. and Vandenplas, Y. (2018). ‘Thickened infant formula: What to know’, Nutrition, vol. 49, no. 1, p. 51-56.
[17]	Orenstein, S. R., Magill, H. L. and Brooks, P. (1987). ‘Thickening of infant feedings for therapy of gastroesophageal reflux’, Journal Paediatrics, vol. 110, no. 2, p. 181-6.
[18]	Vandenplas, Y. and Sacre, L. (1987). ‘Milk-thickening agents as a treatment for gastroesophageal reflux’, Clinical Pediatric (Phila), vol. 26, no. 1, p. 66-8.
[19]	Estevão-Costa, J., Campos, M., Dias, J. A., Trindade, E., Medina, A. M., Carvalho, J. L. (2001). ‘Delayed gastric emptying and gastroesophageal reflux: A pathophysiologic relationship’, Journal of Pediatric Gastroenterol Nutrition, vol. 32, no. 4, p. 471-4.
[20]	Traves, D. (2019). Understanding infant formula. Paediatrics and Child Health.
[21]	Horvath, A., Dziechciarz, P. and Szajewska, H. (2008). ‘The effect of thickened-feed interventions on gastroesophageal reflux in infants: Systematic review and meta-analysis of randomized, controlled trials’, Pediatrics, vol. 122, no. 6, p. 1268-1277.
[22]	González-Bermúdez, C., Frontela-Saseta, C., López-Nicolás, R., Ros-Berruezo, G. and Martínez-Graciá, C. (2014). ‘Effect of adding different thickening agents on the viscosity properties and in vitro mineral availability of infant formula’, Food Chemistry, vol. 159, no. 1, p. 5-11.
[23]	Owens, C., Labuschagne, I. and Lombard, M. (2012). ‘Infant formula for gastro-oesophageal reflux disease’, South African Family Practice, vol. 54, no. 2, p. 106-110.
[24]	Meyer, R., Foong, R., Thapar, N., Kritas, S. and Shah, N. (2015). ‘Systematic review of the impact of feed protein type and degree of hydrolysis on gastric emptying in children’, BMC Gastroenterology, vol. 15.
[25]	National Institute for Health and Care Excellence (2015). Gastro-oesophageal reflux disease in children and young people: Diagnosis and management [Online]. Available at https://www.nice.org.uk/guidance/ng1 (Accessed 27 April 2020).
[26]	Kwok, T., Ojha, S. and Dorling, J. (2017). ‘Feed thickener for infants up to six months of age with gastro-oesophageal reflux’, Cochrane Database of Systematic Reviews.
[27]	Huang, R., Forbes, D. and Davies, M. (2002). ‘Feed thickener for newborn infants with gastroesophageal reflux’, Cochrane Database of Systematic Reviews.
[28]	Duncan, D., Larson, K. and Rosen, R. (2019). ‘Clinical Aspects of Thickeners for Pediatric Gastroesophageal Reflux and Oropharyngeal Dysphagia’, Current Gastroenterology Reports, vol. 21, no. 7, p. 30.
[29]	Moher, D., Shamseer, L., Clarke, M., Ghersi, D., Liberati, A., Petticrew, M., Shekelle, P., Stewart, L. and PRISMA-P Group (2015). ‘Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement’, Systematic Review, vol. 4, no. 1, pp.1-9.
[30]	Higgins, J., Altman, D., Gotzsche, P., Juni, P., Moher, D., Oxman, A., Savovic, J., Schulz, K., Weeks, L. and Sterne, J. (2011). ‘The Cochrane Collaboration's tool for assessing risk of bias in randomised trials’, British Medical Journal.
[31]	Ostrom, K., Jacobs, J., Merritt, R. and Murray, R. (2006). ‘Decreased regurgitation with a soy formula containing added soy fibre’, Clinical Pediatrics, vol. 45, no. 1, p. 29-36.
[32]	Chao, H. and Vandenplas, Y. (2007). ‘Effect of cereal-thickened formula and upright positioning on regurgitation, gastric emptying, and weight gain in infants with regurgitation’, Nutrition, vol. 23, no. 1, p. 23-28.
[33]	Miyazawa, R., Tomomasa, T., Kaneko, H., Arakawa, H. and Morikawa, A. (2007). ‘Effect of formula thickened with reduced concentration of locust bean gum on gastroesophageal reflux’, Acta Paediatrician, vol. 96, no. 6, p. 910-914.
[34]	Vandenplas, Y., Leluyer, B., Cazaubiel, M., Housez, B. and Bocquet, A. (2013). ‘Double-blind comparative trial with 2 antiregurgitation formulae’, Journal of Pediatric Gastroenterology and Nutrition, vol. 57, no. 3, p. 389-393.
[35]	Vandenplas, Y. and De Greef, E. (2014). ‘Extensive protein hydrolysate formula effectively reduces regurgitation in infants with positive and negative challenge tests for cow's milk allergy’, Acta Paediatrician, vol. 103, no. 6, p. 243-250.
[36]	Ummarino, D., Miele, E., Martinelli, M., Scarpato, E., Crocetto, F., Sciorio, E. and Staiano, A. (2015). ‘Effect of magnesium alginate plus simethicone on gastroesophageal reflux in infants: A randomized, open trial’, Digestive and Liver Disease, vol. 46, no. 1, p. 81.
[37]	Indrio, F., Riezzo, G., Giordano, P., Ficarella, M., Miolla, M., Martini, S., Corvaglia, L. and Francavilla, R. (2017). ‘Effect of a partially hydrolysed whey infant formula supplemented with starch and Lactobacillus reuteri DSM 17938 on regurgitation and Gastric Motility’, Nutrients, vol. 9, no. 11, p. 1181.
[38]	Staelens, S., Van Den Driessche, M., Barclay, D., Carrié-Faessler, A., Haschke, F., Verbeke, K., Vandebroek, H., Allegaert, K., Van Overmeire, B., Van Damme, M. and Veereman-Wauters, G. (2008). ‘Gastric emptying in healthy new-borns fed an intact protein formula, a partially and an extensively hydrolysed formula’, Clinical Nutrition, vol. 27, no. 2, p. 264-268.
[39]	Caugant, I., Petit, H., Charbonneau, R., Saovie, L., Toullec, R., Thirouin, S. and Yvon, M. (1992). ‘In vivo and in vitro gastric emptying of protein fractions of milk replacers containing whey proteins’, Journal of Dairy Science, vol. 75, no. 3, p. 847-856.
[40]	Miraglia Del Giudice, M., D’Auria, E., Peroni, D., Palazzo, S., Radaelli, G., Comberiati, P., Galdo, F., Maiello, N. and Riva, E. (2015). ‘Flavour, relative palatability and components of cow’s milk hydrolysed formulas and amino acid-based formula’, Italian Journal of Pediatrics, vol. 41, no. 42.
[41]	Hegar, B., Rantos, R., Firmansyah, A., De Schepper, J. and Vandenplas, Y. (2008). ‘Natural evolution of infantile regurgitation versus the efficacy of thickened formula’, Journal of Pediatric Gastroenterology and Nutrition, vol. 47, no. 1, p. 26-30.
[42]	Greer, F. (2018). ‘Use of starch and modified starches in infant feeding’, Journal of Pediatric Gastroenterology and Nutrition, vol. 66, no. 1, p. 30-34.
[43]	Qi, X., Al-Ghazzewi, F. and Tester, R. (2018). ‘Dietry fibre, gastric emptying and carbohydrate digestion: A mini-review’, Starch – Stärke.
[44]	Niggemann, B., von Berg, A., Bollrath, C., Berdel, D., Schauer, U., Rieger, C., Haschke-Becher, E. and Wahn, U. (2008). ‘Safety and efficacy of a new extensively hydrolysed formula for infants with cow’s milk protein allergy’, Pediatric Allergy and Immunology, vol. 19, no. 4, p. 348-354.